Regulation of p300 via Phosphorylation by PKC-Related Kinase
L. W. Yuan1, L. L. David2, J. E. Gambee3, J. A. Oughton4 & R. H. Goodman1
1Vollum Institute and 2Department
of Oral Molecular Biology, Oregon Health Sciences University, Portland,
OR, USA;
3Protein Structure Facility, Shriners Hospital
for Children, Portland, OR, USA;
4EHS Center, Oregon State University, Corvallis,
OR, USA
Abstract
p300 is a phosphoprotein.
A major phosphorylation site of p300 in HeLa cells is serine 89, which
is highly conserved among human and mouse p300 and CBP. The kinase
responsible for the phosphorylation of serine 89 (S89K) is a protein kinase
C (PKC)-related kinase. Phosphorylation at serine 89 by this kinase
inhibits the p300 histone acetyltransferase (HAT) and transcriptional activities.
It also represses estrogen receptor (ER)-mediated transactivation that
is potentiated by p300. This inhibition of the ER activity through
the phosphorylation of p300 at serine 89 implies a barrier to the cell
cycle progression at G1, and thus correlates with the physiological
role of p300 in assisting cells to withdraw from the cell cycle and further
inducing differentiation.